We find that, for a range of agonist concentration, Ca2+ dynamics in ER-mitochondria nanodomains is essential for maintaining intracellular calcium oscillations. The model predicts faster Ca2+ oscillations when there is an increase in the volume ratio between ER-mitochondrial nanodomains and the cytosol. Moreover, given that the production of adenosine trisphosphate (ATP) and the generation of reactive oxygen species (ROS) are closely associated with mitochondrial Ca2+, the model also provides some insights into the relationship between ER-mitochondria nanodomains Ca2+ dynamics and mitochondrial function. We investigate, computationally, strategies for alleviating the progress of dysfunction associated with aberrant Ca2+ dynamics.